2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

24.68 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

1 234.2 mg/m³

Explanation for the modification of the dose descriptor starting point:

No data on systemic toxicity after inhalation is available. Derivation of the long term inhalation DNEL is done on the basis of the corresponding long term oral DNEL from a repeated dose oral toxicity study (OECD 422).

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

4

Justification:

As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of 55 days (males) up to 67 days (females) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.

AF for interspecies differences (allometric scaling):

1

Justification:

Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences

AF for intraspecies differences:

5

Justification:

The default value for the relatively homogenous group "worker" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

14 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

2 800 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No data on systemic toxicity after dermal exposure is available. Derivation of the long term dermal DNEL is done on the basis of the corresponding long term oral DNEL from a repeated dose oral toxicity study (OECD 422).

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

4

Justification:

As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of 55 days (males) up to 67 days (females) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

5

Justification:

The default value for the relatively homogenous group "worker" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

General

DNEL derivation for the test substance is performed under consideration of the recommendations of ECHA. In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

 

Workers – Hazard via inhalation route

 

Long term systemic inhalation DNEL, worker

The DNEL long term, systemic (inhalation) is derived by route-to route extrapolation from the repeated dose oral toxicity study.

 

Step 1: Selection of the relevant dose descriptor (starting point):

The repeated dose oral toxicity study (OECD 422) is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral NOAEL is 1000 mg/kg bw/day.

 

Step 2: Modification into a correct starting point:

Using a conservative approach, a worker DNEL (long term inhalation exposure) is derived considering a two times higher absorption via inhalation (100 %) than oral (50 %) absorption.

 

Relevant dose descriptor (NOAEL): 1000 mg/kg bw/day

Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/d

Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat 50 % / ABSinh-human 100 %): 0.5

Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m³

Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³

Frequency of exposure in study: 7 days/week

Frequency of worker exposure: 5 days/week

 

Corrected inhalatory NOAEC for workers

= 1000 mg/kg bw/day * 0.5 * (1 / 0.38 m³/kg bw/day) * (6.7 m³/10 m³) * (7/5)

= 1234.2 mg/m³

 

Step 3: Use of assessment factors: 50

Interspecies: Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation. 

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Exposure duration AF: 4

Remaining uncertainties AF: 1

 

In conclusion, long term systemic inhalation DNEL, workers = 24.68 mg/m3

 

 

Short term systemic inhalation DNEL, worker

No experimental data on acute inhalation toxicity of the test substance is available. The substance is not classified for acute oral toxicity, therefore no adverse result for inhalation toxicity is expected (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). Thus, no DNEL is required.

 

 

Short and long term local inhalation DNEL, worker

No data on local toxicity after inhalation is available. Data on acute and long term local toxicity after oral application is available and showed no specific local effects.In addition the vapour pressure shows unlikely availability of the substance as an inhalable vapour. Therefore no adverse effects on the respiratory system are expected. Thus, no DNEL local, long-term and acute (inhalation) is required (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8).

 

 

 

Workers – Hazard via dermal route

Long term systemic dermal DNEL, worker

The DNEL long term, systemic (dermal) is derived by route-to route extrapolation from the repeated dose oral toxicity study.

 

Step 1: Selection of the relevant dose descriptor (starting point):

The repeated dose toxicity study (OECD 422) is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral NOAEL is 1000 mg/kg bw/day.

 

Step 2: Modification of the starting point:

The logPow of the test substance was determined to be -2. Therefore the dermal uptake is considered to be 50 % of the oral uptake in the worst case.

 

Factor for dermal NOAEL= 100 % oral / 50 % dermal= 2

Frequency of exposure in study: 7 days/week

Frequency of worker exposure: 5 days/week

 

oral NOAEL 1000 mg/kg bw/day * 2 * (7/5) = 2800 mg/kg bw/day dermal NOAEL

 

Step 3: Use of assessment factors: 200

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Exposure duration AF: 4

Remaining uncertainties AF: 1

 

In conclusion, long term systemic dermal DNEL, workers = 14 mg/kg bw/day

 

Short term systemic dermal DNEL, worker

No data for the classification and labelling of the test substance for acute dermal toxicity is available. The substance is not classified for acute oral toxicity, therefore no adverse result for dermal toxicity is expected (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). Thus, no DNEL is required.

 

Short and long term local dermal DNEL, worker

The test material is not classified and labelled for skin sensitization or skin irritation, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

 

Worker – Hazard for the eyes

For exposure to the eyes a low hazard was identified, as the test substance is classified for eye irritation Cat.2according to Regulation (EC) No 1272/2008 (CLP). A qualitative risk assessment is conducted (in accordance with "Guidance on information requirements and chemical safety assessment", Part E).Therefore goggles and further appropriate RMMs are carried into execution.

 

References

(not included as endpoint study record)

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. November 2012.

- ECHA (2017). Guidance on information requirements and chemical safety assessment.Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. June 2017.

- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.

- ECHA (2016). Guidance on information requirements and chemical safety assessment.Part E: Risk Characterisation, Version 3.0, May 2016.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

Since no exposure of the general population is intended or anticipated as the substance is not present in consumer–available products, no DNELs for general population have been derived (in accordance with "Guidance on information requirements and chemical safety assessment", Part E).